Transition from esophagectomy to endoscopic therapy for early esophageal cancer.

BACKGROUND: To assess the outcomes of patients with early esophageal cancer and high-grade dysplasia comparing esophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET). METHODS: Retrospective cohort study of consecutive patients with early esophageal cancer/high-grade dysplasia, treated between 2000 and 2018 at a tertiary center. Primary outcomes were all-cause and disease-specific mortality assessed by multivariable Cox regression and a propensity score matching sub analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, tumor grade (G1/2 vs. G3), tumor stage, and lymphovascular invasion. Secondary outcomes included complications, hospital stay, and overall costs. RESULTS: Among 269 patients, 133 underwent esophagectomy and 136 received EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85, 95% CI 0.73, 4.72) and disease-specific mortality (HR 1.10, 95% CI 0.26, 4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien-Dindo ≥3 26.3% vs. endoscopic therapy 0.74%), longer in-patient stay (median 14 vs. 0 days endoscopic therapy) and higher hospital costs(£16 360 vs. £8786 per patient). CONCLUSION: This series of patients treated during a transition period from surgery to EET, demonstrates a primary endoscopic approach does not compromise oncological outcomes with the benefit of fewer complications, shorter hospital stays, and lower costs compared to surgery. It should be available as the gold standard treatment for patients with early esophageal cancer. Those with adverse prognostic features may still benefit from esophagectomy.

Economic burden of COVID-19, China, January-March, 2020: a cost-of-illness study.

OBJECTIVE: To estimate the economic cost of coronavirus disease 19 (COVID-19) in 31 provincial-level administrative regions and in total, in China. METHODS: We used data from government reports, clinical guidelines and other publications to estimate the main cost components of COVID-19 during 1 January-31 March 2020. These components were: identification and diagnosis of close contacts; suspected cases and confirmed cases of COVID-19; treatment of COVID-19 cases; compulsory quarantine of close contacts and suspected cases; and productivity losses for all affected residents. Primary outcomes were total health-care and societal costs. FINDINGS: The total estimated health-care and societal costs associated with COVID-19 were 4.26 billion Chinese yuan (¥; 0.62 billion United States dollars, US$) and ¥ 2646.70 billion (US$ 383.02 billion), respectively. Inpatient care accounted for 44.2% (¥ 0.95 billion/¥ 2.15 billion) of routine health-care costs followed by medicines, accounting for 32.5% (¥ 0.70 billion/¥ 2.15 billion). Productivity losses accounted for 99.8% (¥ 2641.61 billion/¥ 2646.70 billion) of societal costs, which were mostly attributable to the effect of movement-restriction policies on people who did not have COVID-19. Societal costs were most sensitive to salary costs and number of working days lost due to movement-restriction policies. Hubei province had the highest health-care cost while Guangdong province had the highest societal cost. CONCLUSION: Our results highlight the high economic burden of the COVID-19 outbreak in China. The control measures to prevent the spread of disease resulted in substantial costs from productivity losses amounting to 2.7% (US$ 382.29 billion/US$ 14.14 trillion) of China's annual gross domestic product.

Disease Burden Attributable to the First Wave of COVID-19 in China and the Effect of Timing on the Cost-Effectiveness of Movement Restriction Policies.

OBJECTIVES: Movement restriction policies (MRPs) are effective in preventing/delaying COVID-19 transmission but are associated with high societal cost. This study aims to estimate the health burden of the first wave of COVID-19 in China and the cost-effectiveness of early versus late implementation of MRPs to inform preparation for future waves. METHODS: The SEIR (susceptible, exposed, infectious, and recovered) modeling framework was adapted to simulate the health and cost outcomes of initiating MRPs at different times: rapid implementation (January 23, the real-world scenario), delayed by 1 week, delayed by 2 weeks, and delayed by 4 weeks. The end point was set as the day when newly confirmed cases reached zero. Two costing perspectives were adopted: healthcare and societal. Input data were obtained from official statistics and published literature. The primary outcomes were disability-adjusted life-years, cost, and net monetary benefit. Costs were reported in both Chinese renminbi (RMB) and US dollars (USD) at 2019 values. RESULTS: The first wave of COVID-19 in China resulted in 38 348 disability adjusted life-years lost (95% CI 19 417-64 130) and 2639 billion RMB losses (95% CI 1347-4688). The rapid implementation strategy dominated all other delayed strategies. This conclusion was robust to all scenarios tested. At a willingness-to-pay threshold of 70 892 RMB (the national annual GDP per capita) per disability-adjusted life-year saved, the probability for the rapid implementation to be the optimal strategy was 96%. CONCLUSIONS: Early implementation of MRPs in response to COVID-19 reduced both the health burden and societal cost and thus should be used for future waves of COVID-19.

Protocol for A randomised feasibility trial comparing fluoride interventions to prevent dental decay in older people in care homes (FInCH trial).

BACKGROUND: The number and proportion of older people globally is growing faster than that of any other age group. At the same time the number of people retaining some of their own teeth is rising. There significant differences between those living in care and their community dwelling peers, with evidence showing those in care having fewer teeth and significantly higher levels of dental decay. There are numerous Cochrane reviews linking the use of fluoride to a reduction in dental decay, however, the majority of research on effectiveness has been conducted on children and consequently, children and adolescents tend to be the main recipients of fluoride interventions. There are to date no studies comparing the effectiveness of fluoride interventions in older people in care homes in the UK. However, prior to developing an appropriate protocol for full-scale trial comparing clinical effectiveness of fluoride interventions, there are a number of trial feasibility and statistical parameters that need to be clarified. METHODS: This trial is a single centre, multi-site randomised controlled assessor blind parallel group (three groups) trial, with the primary objective of establishing the feasibility, practicability and compliance of fluoride interventions to prevent dental decay in care homes. Secondary and tertiary objectives will aim to explore the acceptability of the interventions from resident, care home and dental services perspectives, and estimate the efficacy of the three different fluoride treatments. DISCUSSION: This feasibility trial will produce new knowledge and add value to a landscape that is under researched. Although the efficacy of fluoride interventions is proven, the feasibility of dental research and prevention in this vulnerable group and in the complex care home setting is novel. This work will not only add to our understanding of the interface of dental care and social care but will also contribute to our broader understanding on undertaking research in care home settings. Dental care for older people has been a longstanding issue, and the events of this past year has shone a light on the vulnerabilities of those residing in care homes and so this research is landing at a pivotal time. Trial registration EudraCT Registration 2017-002248-34. Registered 20th February 2018 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-002248-34 .

Health State Utility Values in Schizophrenia: A Systematic Review and Meta-Analysis.

OBJECTIVES: Patient preferences are increasingly important in informing clinical and policy decisions. Health-state utility values (HSUVs) are quantitative measures of people's preferences over different health states. In schizophrenia, there is no clarity about HSUVs across the symptoms' severity spectrum. This meta-analysis aims to synthesize the literature on HSUVs in people with schizophrenia. METHODS: We searched Medline, PsycInfo, Embase, EconLit, The Cochrane Library, and specialized databases. The studies reporting HSUVs in people with schizophrenia were selected and pooled in a random-effects meta-analysis. The primary outcome was the mean HSUV obtained from participants. RESULTS: A total of 54 studies involving 87 335 participants were included. The pooled estimate using direct elicitation was a mean HSUV of 0.79 (95% CI: 0.70-0.88) for mild symptomatic states, 0.69 (95% CI: 0.54-0.85) in moderate states, and 0.34 (95% CI: 0.13-0.56) in severe states. Studies using indirect techniques resulted in a pooled mean HSUV of 0.73 (95% CI: 0.67-0.78) applying the EuroQol 5-dimension, 0.66 (95% CI: 0.62-0.71) in the Short-Form 6-dimension, and 0.59 (95% CI: 0.57-0.61) using the Quality of Well-Being scale. All the estimates resulted in considerable heterogeneity, partially reduced by meta-regression. CONCLUSION: Our findings suggest that the severity of psychotic symptoms has an important effect on HSUVs in schizophrenia, with values mirroring patients with disabling physical conditions such as cancer and stroke. Decision makers should be aware of these results when including people's preferences in trials, models, and policy decisions.

Costs of Early Invasive Breast Cancer in England Using National Patient-Level Data.

OBJECTIVES: This study aimed to use patient-level data to provide up-to-date estimates of early invasive breast cancer care costs by stage in England and to explore to what extent these costs varied based on patients' ages and geographic regions. METHODS: This study identified women aged 50 years and older who had been diagnosed with early invasive breast cancer between January 1, 2014, and December 31, 2015, using linked cancer registrations and routine hospital data sets generated from the usual care for all National Health Service trusts in England. Cost estimates were derived from hospital records in Hospital Episodes Statistics with additional chemotherapy and radiotherapy information from the national data sets. We fitted general linear regression models to analyze the cost data. The model that best fit the data was selected using the model selection criteria of Akaike information criterion. RESULTS: 55 662 women with early invasive breast cancer in England were included. The generalized linear model with log-gamma distribution fit the data best. The costs of breast cancer care for 1 year after diagnosis were strongly dependent on stage at diagnosis, controlling for other covariates. The estimated average per-patient hospital-related costs were £5167 at stage I, £7613 at stage II, and £13 330 at stage IIIA. Costs decreased with increasing age (P < .001) and varied across region (P < .001), deprivation level (P < .001), referral source (P < .01), presence of comorbidities (P< .001), and tumor receptor (ER/PR/HER2) status (P < .001). CONCLUSIONS: In England, the costs of breast cancer care increased with advancing stage of the disease at diagnosis. Breast cancer costs varied by age and geographic region.

Cost-effectiveness analysis of English memory assessment services 2 years after first consultation for patients with dementia.

OBJECTIVES: This paper aims to compare changes over 2 years in patients' health-related quality of life (HRQL) with the health and social care costs of diagnosis and treatment of people newly referred to memory assessment services (MAS). METHODS: We analysed observational data from 1318 patients referred to 69 MAS who completed resource use and HRQL questionnaires at baseline 3, 6, 12, and 24 months. We reported mean differences in HRQL (disease-specific DEMQOL and generic EQ-5D-3 L), quality-adjusted life years (QALYs), costs and cost-effectiveness between baseline, and 2-year follow-up. RESULTS: Two years after referral to MAS, patients reported a higher DEMQOL score (mean gain 4.47, 95% confidence interval, 3.08-5.90) and EQ-5D-3 L (0.014, -0.011 to 0.039). Mean total costs and QALYs over 24 months was £2411 (£1721-£2873) and 0.027 (0.003-0.051), respectively. Assuming that patients' HRQL would not have altered over the 2 years had they not attended MAS, these outcomes suggest an incremental cost-effectiveness ratio of £89 546 (£38 123-£145 864) based on changes in EQ-5D-3 L. If we assumed that patients' HRQL would have declined by about 10% over this period had they not attended MAS, the cost-effectiveness ratio would be £25 056. The largest MAS (N = 32; 46%) with over 50 new patients a month were more likely to be cost-effective than smaller ones (P < 0.01). CONCLUSIONS: MAS are effective and can be cost-effective for diagnosing and treating people with suspected dementia. Large variations in costs between clinics suggest that many MAS could improve their cost-effectiveness.

Value of External Data in the Extrapolation of Survival Data: A Study Using the NJR Data Set.

BACKGROUND: Extrapolation of time-to-event data can be a critical component of cost-effectiveness analysis. OBJECTIVES: To contrast the value of external data on treatment effects as a selection aid in model fitting to the clinical data or for the direct extrapolation of survival. METHODS: We assume the existence of external summary data on both treatment and control and consider two scenarios: availability of external individual patient data (IPD) on the control only and an absence of external IPD. We describe how the summary data can be used to extrapolate survival or to assess the plausibility of extrapolations of the clinical data. We assess the merit of either approach using a comparison of cemented and cementless total hip replacement as a case study. Merit is judged by comparing incremental net benefit (INB) obtained in scenarios with incomplete IPD with that derived from modeling external IPD on both treatment and control. RESULTS: Measures of fit with the external summary data did not identify survival model specifications that best estimated INB. Addition of external IPD for the control only did not improve estimates of INB. Extrapolation of survival using the external summary data comparing treatment and control improved estimates of INB. CONCLUSIONS: Our case study indicates that summary data comparing treatment and control are more valuable than IPD limited to the control when extrapolating event rates for cost-effectiveness analysis. These data are best exploited in direct extrapolation of event rates rather than as an aid to select extrapolations on the basis of the clinical data.

The cost of diagnosis and early support in patients with cognitive decline.

OBJECTIVE: Recent research indicates considerable heterogeneity in the provision of memory assessment services (MAS). However, little is known on the extent of variation in the costs of the services MAS provide. We investigated the costs of supporting patients with suspected dementia, including assessment and support over the following 6 months. METHODS: Clinic costs were estimated on the basis of an organisational survey reporting staff roll, grade and activities. Costs of primary health and social care were estimated from questionnaire data reported by carers of patients at baseline, 3 and 6 months after referral. RESULTS: Mean monthly staff costs at MAS were £73 000. Imaging at assessment costs an additional £3500 per month. Monthly clinic cost per new patient assessed varied from £320 to £5400 across clinics. Additional primary health and social care costs of £130-220 a month between baseline and 6 months were reported by carers. Costs of pharmacological and non-pharmacological treatments reported by carers were small. Informal care costs dwarfed health and social care costs when valued at a modest unit cost. The overall mean cost of supporting a patient for 6 months varied from £1600 to £2500 dependent on assumptions regarding the proportion of MAS intervention and review costs accrued at 6 months. CONCLUSIONS: There is considerable variation in the intensity and associated costs of services provided by MAS. Further research should ascertain to what extent such variation is associated with differences in patient outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

Cost-effectiveness of non-surgical periodontal therapy for patients with type 2 diabetes in the UK.

AIM: Periodontal therapy has been shown to reduce glycated haemoglobin in patients with diabetes, although considerable uncertainty remains regarding the sustainability of such changes. We evaluate the cost-effectiveness of non-surgical periodontal therapy and rigorous maintenance treatment in patients with type 2 diabetes and periodontitis from a provider perspective in the UK. METHOD: Lifetime costs relating to periodontal treatment were modelled for a cohort of patients with type 2 diabetes. The projected lifetime impact of changes in glycated haemoglobin on diabetes treatment costs and quality adjusted life expectancy were estimated from a published simulation model. Costs and outcomes were combined to estimate the Incremental Cost-Effectiveness Ratio for periodontal therapy in patients with type 2 diabetes. RESULTS: The Incremental Cost-Effectiveness Ratio was £28,000 per Quality Adjusted Life-Year for a man aged 58 with glycated haemoglobin of 7%-7.9%. The results were particularly sensitive to assumptions on the impact of periodontal therapy on glycated haemoglobin, the proportion of patients who comply with maintenance therapy and the proportion of compliant patients who respond to treatment. CONCLUSION: Assuming improvements in glycated haemoglobin can be maintained, periodontal therapy may be cost-effective for patients with type 2 diabetes at acceptable cost-per-Quality Adjusted Life-Year thresholds in the UK.

Comparing WTP values of different types of QALY gain elicited from the general public.

BACKGROUND: The appropriate thresholds for decisions on the cost-effectiveness of medical interventions remain controversial, especially in 'end-of-life' situations. Evidence of the values placed on different types of health gain by the general public is limited. METHODS: Across nine European countries, 17,657 people were presented with different hypothetical health scenarios each involving a gain of one quality adjusted life year (QALY) and asked about their willingness to pay (WTP) for that gain. The questions included quality of life (QoL) enhancing and life extending health gains, and a scenario where respondents faced imminent, premature death. RESULTS: The mean WTP values for a one-QALY gain composed of QoL improvements were modest (PPP$11,000). When comparing QALY gains obtained in the near future, the valuation of life extension exceeded the valuation of QoL enhancing gains (mean WTP PPP$19,000 for a scenario in which a coma is avoided). The mean WTP values were higher still when respondents faced imminent, premature death (PPP$29,000). CONCLUSIONS: Evidence from the largest survey on the value of health gains by the general public indicated a higher value for life extending gains compared with QoL enhancing gains. A further modest premium may be indicated for life extension when facing imminent, premature death.

Costs and cost-effectiveness of pediatric inguinal hernia repair in Uganda.

BACKGROUND: Surgically treatable diseases contribute approximately 11% of disability-adjusted life years (DALYs) worldwide yet they remain a neglected public health priority in low- and middle-income countries (LMICs). Pediatric inguinal hernia is the most common congenital abnormality in newborns and a major cause of morbidity and mortality yet elective repair remains largely unavailable in LMICs. This study is aimed to determine the costs and cost-effectiveness of pediatric inguinal hernia repair (PIHR) in a low-resource setting. METHODS: Medical costs of consecutive elective PIHRs were recorded prospectively at two centers in Uganda. Decision modeling was used to compare two different treatment scenarios (adoption of PIHR and non-adoption) from a provider perspective. A Markov model was constructed to estimate health outcomes under each scenario. The robustness of the cost-effectiveness results in the base case analysis was tested in one-way and probabilistic sensitivity analysis. The primary outcome of interest was cost per DALY averted by the intervention. RESULTS: Sixty-nine PIHRs were performed in 65 children (mean age 3.6 years). Mean cost per procedure was $86.68 US (95% CI 83.1-90.2 USD) and averted an average of 5.7 DALYs each. Incremental cost-effectiveness ratio was $12.41 per DALY averted. The probability of cost-effectiveness was 95% at a cost-effectiveness threshold of $35 per averted DALY. Results were robust to sensitivity analysis under all considered scenarios. CONCLUSION: Elective PIHR is highly cost-effective for the treatment and prevention of complications of hernia disease even in low-resource settings. PIHR should be prioritized in LMICs alongside other cost-effective interventions.

Cost-effectiveness of health-related lifestyle advice delivered by peer or lay advisors: synthesis of evidence from a systematic review.

BACKGROUND: Development of new peer or lay health-related lifestyle advisor (HRLA) roles is one response to the need to enhance public engagement in, and improve cost-effectiveness of, health improvement interventions. This article synthesises evidence on the cost-effectiveness of HRLA interventions aimed at adults in developed countries, derived from the first systematic review of the effectiveness, cost-effectiveness, equity and acceptability of different types of HRLA role. METHODS: The best available evidence on the cost-effectiveness of HRLA interventions was obtained using systematic searches of 20 electronic databases and key journals, as well as searches of the grey literature and the internet. Interventions were classified according to the primary health behaviour targeted and intervention costs were estimated where necessary. Lifetime health gains were estimated (in quality-adjusted life years, where possible), based on evidence of effectiveness of HRLAs in combination with published estimates of the lifetime health gains resulting from lifestyle changes, and assumptions over relapse. Incremental cost-effectiveness ratios are reported. RESULTS: Evidence of the cost-effectiveness of HRLAs was identified from 24 trials included in the systematic review. The interventions were grouped into eight areas. We found little evidence of effectiveness of HRLAs for promotion of exercise/improved diets. Where HRLAs were effective cost-effectiveness varied considerably: Incremental Cost effectiveness Ratios were estimated at £6,000 for smoking cessation; £14,000 for a telephone based type 2 diabetes management; and £250,000 or greater for promotion of mammography attendance and for HIV prevention amongst drug users. We lacked sufficient evidence to estimate ICERs for breastfeeding promotion and mental health promotion, or to assess the impact of HRLAs on health inequalities. CONCLUSIONS: Overall, there is limited evidence suggesting that HRLAs are cost-effective in terms of changing health-related knowledge, behaviours or health outcomes. The evidence that does exist indicates that HRLAs are only cost-effective when they target behaviours likely to have a large impact on overall health-related quality of life. Further development of HRLA interventions needs to target specific population health needs where potential exists for significant improvement, and include rigorous evaluation to ensure that HRLAs provide sufficient value for money.

Cost-effectiveness of personalized plaque control for managing the gingival manifestations of oral lichen planus: a randomized controlled study.

AIM: To undertake cost-effectiveness and cost-benefit analyses of an intervention to improve oral health in patients presenting with the gingival manifestations of oral lichen planus (OLP). MATERIALS & METHODS: Eighty-two patients were recruited to a 20-week randomized controlled trial. The intervention was personalized plaque control comprising powered tooth brushing and inter-dental cleaning advice. The primary outcome measure was the oral health impact profile (OHIP) with secondary outcomes of pain, plaque index, mucosal disease score and cost-effectiveness. Private cost data and stated willingness-to-pay (WTP) values for treatment were obtained from intervention patients at 20 weeks. RESULTS: Overall, 81% of intervention patients showed improvement in both plaque index and mucosal disease score at 20 weeks compared to 30% of controls that continued with their usual plaque control regimen. All intervention group patients stated a positive WTP value. The mean net value of the treatment was £172 compared to the incremental cost of the treatment estimated at £122.75. The cost-effectiveness analysis resulted in an incremental cost-effectiveness ratio of £13 per OHIP point. CONCLUSIONS: The tailored plaque control programme was more effective than control in treating the gingival manifestations of oral lichen planus. The programme is cost effective for modest values placed on a point on the OHIP scale and patients generally valued the treatment in excess of the cost.

Foucault and Hayek on public health and the road to serfdom.

This paper draws on the work of Michel Foucault and Friedrich Hayek to understand threats to personal and enterprise freedom, arising from public health governance. Whereas public choice theory examines the incentives these institutions provide to agents, the analysis here understands those incentives as framed by discursive social constructions that affect the identity, power, and positionality of different actors. It shows how overlapping discourses of scientific rationalism may generate a 'road to serfdom' narrowing freedom of action and expression across an expanding terrain. As such, the paper contributes to the growing literature emphasising the importance of narratives, stories and metaphors as shaping political economic action in ways feeding through to outcomes and institutions.

Associations between neighbourhood social cohesion and subjective well-being in two different informal settlement types in Delhi, India: a quantitative cross-sectional study.

OBJECTIVES: To evaluate the relationships between neighbourhood cohesion and subjective well-being (SWB) in two different informal settlement types. DESIGN: Cross-sectional analysis of a community-based survey. SETTING: Communities in two districts, Sanjay Colony, Okhla Phase II and Bhalswa in Delhi, India. PARTICIPANTS: 328 residents in Bhalswa and 311 from Sanjay Colony. MEASUREMENTS: Neighbourhood social cohesion scale measured on an 18-point scale and the SWB scale made up of four subjective measures-hedonic, eudaemonic, evaluative and freedom of choice. Sociodemographic characteristics and trust were used as covariates. RESULTS: In both neighbourhood types there was a statistically significant positive bivariate correlation between neighbourhood cohesion and SWB (Sanjay: r=0.145, p<0.05; Bhalswa: r=0.264, p<0.01). Trust and neighbourhood cohesion were strongly correlated (Sanjay: r=0.618, p<0.01; Bhalswa: r=0.533, p<0.01) and the longer the resident had lived in the community the greater the feeling of neighbourhood cohesion (Sanjay: r=0.157, p<0.01; Bhalswa: r=0.171, p<0.05). Only in the resettlement colony (Bhalswa) was SWB negatively correlated with length of residency (r=-0.117, p<0.05). Residents who chose their settlement type (Sanjay residents) were 22.5 percentage points (pp) more likely to have a feeling of belonging to their neighbourhood than residents that had been resettled (Bhalswa) (Cohen's d effect size 0.45). Sanjay residents had a greater likelihood to feel more satisfied with life (4.8 pp, p<0.01) and having greater perceived freedom of choice (4.8 pp, p<0.01). CONCLUSIONS: Our findings contribute to the general knowledge about neighbourhood cohesion and SWB within different informal settlement types in a mega-city such as New Delhi, India. Interventions that promote sense of belonging, satisfaction with life and freedom of choice have the potential to significantly improve people's well-being.

Should compromised first permanent molar teeth in children be routinely removed? A health economics analysis.

OBJECTIVE: To evaluate the cost-effectiveness of retaining one or more compromised first permanent molars (cFPMs) affected by dental caries or enamel hypomineralization, compared to timely extraction, in children aged 8 years. METHODS: A Markov model was developed to simulate the lifetime of a cFPM. Two management strategies were compared: extraction facilitating spontaneous space closure or maintenance of teeth with restorations. Ten health states were utilized to capture long-term outcomes including various tooth restorations, prostheses or a retained gap at the cFPM site. Outcomes were expressed as Quality Adjusted Tooth-Years (QATYs). The model was informed by survey data on patient preferences for treatment outcomes and UK data on costs. Discounted costs and QATYs were calculated over 62 years. RESULTS: Regardless of the number of cFPMs, retaining cFPMs was more effective than early removal, generating an additional 2.3 QATYs per cFPM. Early removal of one or two cFPM under general anaesthetic (GA) was more expensive than retention and hence never cost-effective. Retaining a cFPM was more expensive than early removal under local anaesthesia or where four cFPMs were extracted under GA. In these cases, retaining cFPMs was cost-effective if a QATY was valued at £100 or £35, respectively. Results were robust to sensitivity analysis. CONCLUSION: Preserving a cFPM was more cost-effective than the early loss of one, or two cFPMs under GA. Preservation of four cFPMs was cost-effective if sufficient value was placed on a QATY. These findings can guide clinical practice on management of cFPMs alongside patient/payer values on maintaining teeth.

Pharmacokinetics and pharmacodynamics of intranasal and intramuscular administration of naloxone in working dogs administered fentanyl.

BACKGROUND: Working dogs exposed to narcotics might require reversal in the field. OBJECTIVE: To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs. ANIMALS: Ten healthy, working dogs aged 1.7 ± 1 year and weighing 26 ± 3 kg. METHODS: In this randomized, controlled cross-over study dogs received either 4 mg of naloxone IN or IM 10 minutes after fentanyl (0.3 mg IV) administration. Sedation was assessed at baseline and 5 minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120 minutes after reversal with naloxone. Blood samples for naloxone detection were obtained at 0, 5, 10, 30, 60 and 120 minutes. Pharmacokinetic parameters and sedation scores were compared between IM and IN naloxone groups. RESULTS: There was a significant increase in sedation score from baseline (0.25 [-4 to 1] IM; 0 [-2 to 1] IN) after fentanyl administration (11 [5-12] IM; 9.25 [4-11] IN), followed by a significant reduction at 5 (0.5 [-0.5 to 1.5] IM; 1.25 [-1.5 to 4.5] IN) through 120 minutes (-0.5 [-2 to 1] IM; 0 [-4.5 to 1] IN) after reversal with naloxone. Route of administration had no significant effect on sedation score. Maximum plasma concentration was significantly lower after IN administration (11.7 [2.8-18.8] ng/mL IN, 36.7 [22.1-56.4] ng/mL IM, P < .001) but time to reach maximum plasma concentration was not significantly different from IM administration. CONCLUSION AND CLINICAL IMPORTANCE: Although IM administration resulted in higher naloxone plasma concentrations compared to IN, reversal of sedation was achieved via both routes after administration of therapeutic doses of fentanyl.